Permanent changes in brain genes may not be so permanent after all

January 27, 2014, Johns Hopkins University School of Medicine
DNA

In normal development, all cells turn off genes they don't need, often by attaching a chemical methyl group to the DNA, a process called methylation. Historically, scientists believed methyl groups could only stick to a particular DNA sequence: a cytosine followed by a guanine, called CpG. But in recent years, they have been found on other sequences, and so-called non-CpG methylation has been found in stem cells, and in neurons in the brain.

Now, a team of researchers at Johns Hopkins has discovered that non-CpG methylation occurs later and more dynamically in neurons than previously appreciated, and that it acts as a system of gene regulation, which can be independent of traditional CpG methylation.

In a study described in the January 28 issue of Nature Neuroscience, the Hopkins team describes this new gene control mechanism and how it may contribute to Rett Syndrome, a nervous system disorder affecting mostly girls that causes problems with movement and communication.

The team, led by Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine's Institute for Cell Engineering's Stem Cell Program, had found non-CpG methylation prevalent in neurons, a finding that surprised them, since this wasn't found in any other cells besides stem cells.

By looking at what genes were being transcribed in neurons, he and his colleagues found that, like the form of methylation scientists had seen in , non-CpG methylation stops genes from being expressed. They also mapped the genome to find where non-CpG methylation happens, and found that it carves out its own niche, and are distributed in regions without CpG methlyation. "That was the first hint that maybe it can function independently of CpG methylation," Song says.

The new kind of methylation also seems to operate under different rules. Scientists have long thought methylation was final. Once a cytosine gets a methyl stuck to it, so the story went, that gene is shut off forever. "This became dogma," Song says. "Once cells become the right type, they don't change their identity or DNA methylation."

But non-CpG methylation seems to happen later, when the neuron is mature—and even after conventional wisdom said it was irreversible. The researchers learned this from an experiment in which they knocked out in adult mice the enzymes that attach methyl groups to DNA. They found the still had just as much CpG methylation, but the non-CpG methylation dropped off. This suggests that non-CpG methylation is an active process, Song says, with methyl groups continually being taken off and put back on, adding to evidence that non-CpG methylation may play more of a role in managing operations in mature .

The researchers also found a way that non-CpG methylation is similar to CpG methylation in one important way: it's read by MeCP2, an enzyme long identified as a player in methylation.

That's significant because a mutation in MeCP2 causes Rett Syndrome, and understanding DNA methylation is key to understanding this syndrome. The disorder occurs, Song says, when working copies of the gene for MeCP2 are silenced during development.

Explore further: Deciphering the cellular reading system of DNA methylation

More information: www.nature.com/neuro/journal/v … nt/full/nn.3607.html

Related Stories

Deciphering the cellular reading system of DNA methylation

April 12, 2013
(Medical Xpress)—Scientists from the FMI identify how a family of proteins reads the methylation marks on the DNA so critical for cell development. These MBD proteins bind directly to methylation marks and inactivate the ...

Methylation linked to metabolic disease

November 11, 2013
(Medical Xpress)—In the first in-depth analysis of DNA methylation in fat, a process that affects the regulation of genes, researchers have linked regions of methylation to metabolic traits such as high body mass index ...

New prostate cancer drugs may not be targeting root cause of disease, scientists warn

January 27, 2014
(Medical Xpress)—New drugs being developed for the treatment of prostate cancer may not be targeting the root cause of the disease, according to research published today (Friday, 24 January 2014) in Cell Death & Differentiation.

Linking risk factors and disease origins in breast cancer

November 20, 2013
Researchers from the Geisel School of Medicine at Dartmouth have found that epigenetic changes to DNA are associated with aging in disease-free breast tissues and are further altered in breast tumors. Epigenetic changes describe ...

Controlling patterns of DNA methylation

October 28, 2011
A study performed by scientists in Dirk Schübeler's team at the Friedrich Miescher Institute for Biomedical Research in Basel identifies DNA sequences that autonomously determine DNA methylation patterns. Genomic patterns ...

Recommended for you

When the eyes move, the eardrums move, too

January 23, 2018
Simply moving the eyes triggers the eardrums to move too, says a new study by Duke University neuroscientists.

Cognitive training helps regain a younger-working brain

January 23, 2018
Relentless cognitive decline as we age is worrisome, and it is widely thought to be an unavoidable negative aspect of normal aging. Researchers at the Center for BrainHealth at The University of Texas at Dallas, however, ...

Lifting the veil on 'valence,' brain study reveals roots of desire, dislike

January 23, 2018
The amygdala is a tiny hub of emotions where in 2016 a team led by MIT neuroscientist Kay Tye found specific populations of neurons that assign good or bad feelings, or "valence," to experience. Learning to associate pleasure ...

Your brain responses to music reveal if you're a musician or not

January 23, 2018
How your brain responds to music listening can reveal whether you have received musical training, according to new Nordic research conducted in Finland (University of Jyväskylä and AMI Center) and Denmark (Aarhus University).

New neuron-like cells allow investigation into synthesis of vital cellular components

January 22, 2018
Neuron-like cells created from a readily available cell line have allowed researchers to investigate how the human brain makes a metabolic building block essential for the survival of all living organisms. A team led by researchers ...

Finding unravels nature of cognitive inflexibility in fragile X syndrome

January 22, 2018
Mice with the genetic defect that causes fragile X syndrome (FXS) learn and remember normally, but show an inability to learn new information that contradicts what they initially learned, shows a new study by a team of neuroscientists. ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

JVK
not rated yet Jan 28, 2014
In the mouse model of Rett syndrome the changes are nutrient-dependent. This links the epigenetic effects of choline to intercellular signaling, amino acid substitutions, and stochastic expression of newly created genes in the mouse-to-human model of nutrient-dependent pheromone-controlled amino acid substitutions, de novo creation of genes and chromosomal rearrangements.

I used the mouse-to-human model as an example with other examples of ecological adaptations that refute the theory of mutation-driven evolution. My model shows that mutation-initiated natural selection is not biologically plausible or ecologically valid because mutations perturb the protein folding required for increased organismal complexity.

http://www.socioa...53/27989

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.